26/10/2015 Tetracyclines

OfficialreprintfromUpToDate
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Tetracyclines

Author SectionEditor DeputyEditor

DByronMay,PharmD,BCPS DavidCHooper,MD JenniferMitty,MD,MPH

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Sep2015.|Thistopiclastupdated:Jul23,2014.
INTRODUCTIONChlortetracyclinewasthefirsttetracyclinediscovered,in1948.Sincethenfiveadditional
tetracyclineshavebeenisolatedorderived(oxytetracycline,tetracycline,demeclocycline,doxycyclineand
minocycline),butonlythelastfourareavailableforsystemicuseintheUnitedStates.Ofthesefouragents,
doxycyclineandminocyclinearethemostfrequentlyprescribed.Researchtofindtetracyclineanalogueslead
tothedevelopmentoftheglycylcyclines.Tigecyclineisthefirstofthisnewclassofagentsandexhibitsbroad
spectrumantibacterialactivitysimilartothetetracyclines[1].

Doxycyclineisoneofthemostactivetetracyclinesandisthemostoftenusedclinicallysinceitpossesses
manyadvantagesovertraditionaltetracyclineandminocycline.Doxycyclinecanbeadministeredtwicedaily,
hasbothintravenous(IV)andoral(PO)formulations,achievesreasonableconcentrationsevenifadministered
withfood,andislesslikelytocausephotosensitivity[2].Doxycyclinemaybeanalternativeforuseinchildren
sinceitbindscalciumtoalesserextentthantetracycline,whichcancausetoothdiscolorationandbony
growthretardation.

MECHANISMOFACTIONThetetracyclinesenterthebacterialcellwallintwoways:passivediffusion
andanenergydependentactivetransportsystem,whichisprobablymediatedinapHdependentfashion.
Onceinsidethecell,tetracyclinesbindreversiblytothe30Sribosomalsubunitatapositionthatblocksthe
bindingoftheaminoacyltRNAtotheacceptorsiteonthemRNAribosomecomplex.Proteinsynthesisis
ultimatelyinhibited,leadingtoabacteriostaticeffect[3].

RESISTANCEIncontrasttomanyotherantibiotics,tetracyclinesareinfrequentlyinactivatedbiologicallyor
alteredchemicallybyresistantbacteria.Resistancetotheseagentsdevelopsprimarilybypreventing
accumulationofthedruginsidethecelleitherbydecreasinginfluxorincreasingefflux.Onceresistance
developstooneofthedrugsinthisclass,itistypicallyconferredtoalltetracyclines.

However,therearedifferencesinresistanceamongspeciesofbacteria.Resistancegenestotetracyclines
oftenoccuronplasmidsorothertransferableelementssuchastransposons[4].Bacteriacarryingaribosome
protectiontypeofresistancegeneproduceacytoplasmicproteinthatinteractswiththeribosomesandallows
theribosomestoproceedwithproteinsynthesiseveninthepresenceofhighintracellularlevelsofthedrug
[4,5].

Tigecyclinehasareducedpotentialforresistance,asitisnotaffectedbythetwomajormechanismsof
tetracyclineresistance:ribosomalprotectionproteinsandeffluxpumps[6].Thus,tigecyclinemayhaveactivity
againsttetracyclineresistantorganisms[7,8].

SPECTRUMOFACTIVITYTheantimicrobialactivityofallthetetracyclinesisessentiallythesame
althoughsomedifferencesintherelativedegreeofactivityagainstcertainpathogensdoexistamongthe
variousagents(table1).Asanexample,minocyclineappearstobethemostactiveofthecompoundsdueto
itsslightincreaseinlipidsolubility.Doxycyclinefollowscloselybehind.

Thetetracyclinesareconsideredbroadspectrumbacteriostaticantibioticsthatareusedtotreatinfection
causedbymanyaerobicgrampositiveandgramnegativebacteria.However,theyalsohaveactivityagainst
manyatypicalpathogens,includingRickettsiaspp.,Borreliaspp.,Coxiellaburnetii,Treponemaspp.,
Chlamydiaspp.,Mycoplasmapneumoniae,Plasmodiumspp.,Vibriocholerae,Vibriovulnificus,Brucellaspp.,
Calymmatobacteriumgranulomatis,Leptospira,Borreliaburgdorferi,Borreliarecurrentis,Burkholderia
pseudomallei,Mycobacteriummarinum,andEntamoebahistolytica.Thesedrugshavelittleactivityagainst
fungiandviruses[9].

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AgainstN.gonorrhoeae,the2006GonococcalIsolateSurveillanceProject(GISP)reportshowsthat25.6
percentofisolatescollectedin2006wereresistanttopenicillin,tetracycline,ciprofloxacin,orsome
combinationofthoseantibiotics[10].Therefore,useoftetracyclinesforthetreatmentofN.gonorrhoeaeinthe
USisNOTrecommendedbytheCDC.

DoxycyclineiseffectiveforpatientswithnongonococcalurethritiscausedbyChlamydiatrachomatishowever,
recurrenturethritisinpatientspreviouslytreatedwithdoxycyclinemaybetheresultoftetracyclineresistantU.
urealyticum.DoxycyclineisanalternativeagentinthetreatmentofgenitalChlamydialinfections[11].

Tigecyclinehasabroaderspectrumofactivitywhencomparedtothetetracyclines.Tigecyclinehasactivity
againstgrampositivepathogensincluding:Enterococcusspp.,vancomycinresistantenterococci(VRE),
Listeria,Streptococcusspp.,bothmethicillinsusceptibleandresistantS.aureus,andS.epidermidis.Its
gramnegativeactivityincludes:Acinetobacterbaumannii,Citrobacterspp.,Enterobacterspp.,Escherichia
coli,Klebsiellaspp.,Pasteurellamultocida,Serratiamarcescens,andStenotrophomonasmaltophilia[6,7].

PHARMACODYNAMICS/PHARMACOKINETICSInanimalstudies,the
pharmacokinetic/pharmacodynamicparameterthatmostcloselycorrelateswiththeefficacyoftetracyclinesis
the24hourratiooftheareaundertheconcentrationversustimecurve(AUC)totheminimuminhibitory
concentration(MIC).AfterexposureofStaphylococcusaureustothetetracyclinesatfivetimestheMICfor
twohours,apostantibioticeffectlastingforthreehourshasbeenobserved[12].

CombinationoftetracyclinesandpenicillinsAdeleteriouseffectwasobservedforthecombinationofa
staticandcidalantibioticwhenchlortetracyclineandpenicillinwereusedtogetherforthetreatmentof
pneumococcalmeningitis.Thecombinationofthetwodrugswasinferiortopenicillinalone.Tetracycline
administeredwithampicillinoramoxicillinmayresultindiminishedbactericidalactivityofthepenicillin.Thus,
combinationsoftetracyclinesandpenicillinsshouldbeavoided,ifpossible.

AbsorptionofthetetracyclinesAbsorptionoftetracyclinesoccursprimarilyintheproximalsmallintestine
andthestomach.Thebioavailabilityoforaldoxycyclineapproaches95percent(withorwithoutfood),with
peakserumconcentrationsseenonetothreehoursafterthedose.Bycontrast,thebioavailabilityoforal
tetracyclineisreducedby50percentifitistakenwithfood.Theabsorptionofalltetracyclinescanbe
decreasedwiththeconcomitantadministrationofmultivalentcations(ie,aluminum,calcium,iron,magnesium).
Thesecationschelatewiththetetracyclinesimpairingtheirabsorption.Concurrentadministrationofproducts
containingdivalentortrivalentcationsshouldbeavoidedwithalltetracyclineswiththepossibleexceptionof
doxycycline[13].

SerumconcentrationsThemaximumserumconcentrationafteranintravenousdoseofdoxycyclineoccurs
within30minutesaftertigecycline,withinonehour.Peakconcentrationsofdoxycyclinerangefrom1.5to2.5
mcg/mLafteradoseof200mgorallyand4to10mcg/mLforthesamedoseadministeredintravenously.
Doxycyclinehasanapparentvolumeofdistributionof50litersandis90percentproteinbound.

DistributionIngeneral,tetracyclinespenetrateintotissuesandbodyfluidsfairlywell.Amongthefollowing
agents,thedegreeoftissuepenetrationcorrelatestolipidsolubility:minocycline>doxycycline>
tetracycline[14].

Fordoxycycline,therapeuticconcentrationshavebeenfoundintheaqueoushumour,CSF(11to56percentof
serumconcentrations),peritonealfluid,tears,lungs,sinuses,digestiveandbiliarytracts,kidney,liver,and
prostate[1416].Doxycyclinealsodistributesintothebone,fat,andmuscleatconcentrationsbelowplasma
levels[15].

Tetracyclinedistributeswellintoasciticfluid,bile,CNS(10to26percent),sinuses,pleuralandsynovialfluid
[14].

Minocyclinehasbeenfoundintherapeuticconcentrationsintheaqueoushumor,bile,duodenum,fallopian
tubes/ovaries,liver,lung,sinuses,saliva,sputum,tears,andthyroidgland.Minocyclinedistributesinlower
concentrationstothebladder,breast,lymphnodes,prostate,andskin[14,15].

Tigecyclinedistributeswellintothebile,CSF,andlung.Animaldatademonstratethattigecyclinedistributes
wellintobone,bonemarrow,spleen,andthyroid[15,17].
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Inaddition,allthetetracyclinescrosstheplacentaandaccumulateintheboneandteethofthefetus.The
tetracyclinesarealsoexcretedinbreastmilk,althoughcomplexationwithcalciuminbreastmilklimits
availabilitytothebreastfedinfant[14].

RoutesofeliminationTheroutesofeliminationdifferamongthetetracyclines.Theprimaryrouteof
eliminationfortetracyclineisthekidneyviaglomerularfiltration.Doxycyclineisprimarilyeliminatedinthe
intestinaltract,withupto90percentofthedoseexcretedinthefeces.Approximately20percentofa
doxycyclinedoseiseliminatedbyglomerularfiltration.Tigecyclineiseliminatedthroughthefecesas
unchangeddrug.

Doseadjustmentisnotnecessaryfordoxycyclineortigecyclineinpatientswithrenaldysfunction,andthus,
thesearethepreferredtetracyclinesinthispopulation[13].Doseadjustmentisonlyrequiredinseverehepatic
dysfunctionfordoxycyclineandtigecycline(maintenancedose25mgIVevery12hours)[6].Minocyclineis
metabolizedinthelivertoatleastsixinactivemetabolites.Only4to9percentofminocyclineisexcretedvia
thekidneys,andfecalconcentrationsarealsominimal.Noaccumulationofminocyclineisseenwithhepatic
failure.Similartodoxycycline,foodhaslittleeffectontheabsorptionofminocycline.Thetetracyclinesare
minimallyremovedbyhemodialysis,peritonealdialysis,orhemofiltrationtherefore,doseadjustmentsarenot
necessaryinthesesituations[13].

SPECIALPOPULATIONS

PregnantorbreastfeedingwomenTetracyclinescancausefetaltoxicitywhengiventopregnantwomen.
Forcertaininfections,thepotentialrisksmaybeoffsetbythebenefits.However,tetracyclinesshould
generallynotbeusedinpregnantwomenorchildrenundertheageofeightyearsunlessotherappropriate
drugsareineffectiveorcontraindicated.

Tetracyclinescrosstheplacentaandachieveconcentrationsinumbilicalcordplasmaandamnioticfluidof60
and20percent,respectively,oflevelsinthematernalcirculation.Thiscancauseaccumulationinfetalbone
andteeth.Tetracyclinesarefoundinhighconcentrationsinhumanbreastmilk,butconcentrationsareverylow
inbreastfedinfants,whichisprobablyareflectionofchelationbycalciuminbreastmilk[13].

RenalfailureTheseagents,withthepossibleexceptionofdoxycyclineandtigecycline,shouldgenerally
notbeusedinpatientswithendstagerenaldisease(table2)[2].

ADVERSEREACTIONSTetracyclinesaregenerallysafedrugs,butsomeadverseeffectscanoccur.

Thefollowingprovidesabriefsummaryofsomeofthemajoradverseeffectsassociatedwithtetracyclines.
Theseissuesarediscussedindetailseparately.SeeTetracyclinedruginformation,Doxycyclinedrug
information,Minocyclinedruginformation,Tigecyclinedruginformation,andDemeclocyclinedruginformation.

GastrointestinalDoserelatedgastrointestinalsideeffectsarethemostcommoncomplaintinpatients
takingoraltetracyclinesandintravenoustigecycline[1].Theseincludeabdominaldiscomfort,epigastricpain,
nausea,vomitingandanorexia.Foodmaydecreasethesesymptomsbutalsomaydecreasetheabsorptionof
tetracyclineby50percent.Fooddoesnotaffecttheabsorptionofdoxycycline.

Tetracyclinesmayaltergutfloratocauselargebulkystoolsanddiarrhea.Diarrheausuallysubsidesoncethe
agentisstopped.Apatientwithcontinueddiarrhea,fever,andarisingwhitebloodcountshouldbeevaluated
forantibioticassociateddiarrheacausedbyClostridiumdifficile.Esophagealulcerationsandstrictureshave
beenreportedwithtetracyclinesbutcanbepreventedbytakingthedrugswithplentyofwaterandnotbefore
bedtime.(See"Clostridiumdifficileinfectioninadults:Clinicalmanifestationsanddiagnosis".)

AllergicandskinreactionsHypersensitivityreactionscanoccurwithtetracyclinesbutareuncommon.Ifa
patientisallergictoonetetracycline,theyshouldbeconsideredallergictoall.Photosensitivityreactionscan
occur,rangingfromaredrashtoblisteringonareasexposedtothesun.Thesereactionsaremostcommon
withdemeclocyclinebutcanoccurwithallanalogues.Photosensitivitycanbedecreasedbyavoidingdirect
sunlightorwearingprotectiveclothingwithsunscreen[2].

TeethandboneTetracyclinescancauseabrowntoyellowdiscolorationoftheteethinchildrenunderthe
ageofeightthatissometimesassociatedwithhypoplasiaoftheenamel.Thedarkeningeffectonthe

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permanentteethappearstobedoserelatedanddoesnotoccurinadults.Theseagentsgenerallyshouldbe
avoidedinchildrenundertheageofeighthoweveriftheymustbeused,doxycyclinemaybethepreferred
agent.Tetracyclinesmayalsodepositinthebonelikelyduetochelateformationwithcalcium,thusadding
anotherreasontoavoidtheseagentsinchildrenwithdevelopingboneformation[2].

LiverandrenalHepatotoxicitywithtetracyclinesisrarebutcanbefatal.Thisoccursmorecommonlywith
tetracyclineandminocyclineandlessoftenwithdoxycycline[18].

Tetracyclinesinhibitproteinsynthesisandmayexacerbatepreexistingrenalfailurebyincreasingtheazotemia
fromaminoacidmetabolism.Demeclocyclinecancauseanephrogenicdiabetesinsipidus,asideeffectthatis
usedtherapeuticallytotreatthesyndromeofinappropriateantidiuretichormonesecretion(SIADH).Theuseof
outdatedtetracyclineshasbeenassociatedwithareversibleFanconilikesyndromeandrenaltubularacidosis
however,currentformulations,whichdonotcontaincitricacidasanexcipient,havevirtuallyeliminatedthis
possibility[2].(See"Treatmentofhyponatremia:Syndromeofinappropriateantidiuretichormonesecretion
(SIADH)andresetosmostat".)

MortalityTigecyclinehasbeenassociatedwithincreasedmortalitywhencomparedwithotherantibacterial
drugs.InSeptember2010,theUSFoodandDrugAdministration(FDA)issuedasafetyannouncement
regardingincreasedmortalitywiththeuseoftigecyclineinpatientswithhospitalacquiredpneumonia(HAP)
[19].A2013analysisof10clinicaltrialsshowedanincreasedriskofdeathinpatientsreceivingtigecyclinefor
FDAapproveduses,includingcommunityacquiredbacterialpneumonia,complicatedskinandskinstructure
infections,andcomplicatedintraabdominalinfections(2.5versus1.8percent,adjustedriskdifference0.6
percent)[2].TheFDAhassubsequentlyaddedaboxedwarningstatingthattigecyclineshouldbereservedfor
useinsituationswhenalternativeagentsarenotsuitable[20].(See"Treatmentofcommunityacquired
pneumoniainadultswhorequirehospitalization",sectionon'Tigecycline'and"Treatmentofhospitalacquired,
ventilatorassociated,andhealthcareassociatedpneumoniainadults",sectionon'Otheragents'.)

MiscellaneousAJarischHerxheimertypereaction(JHR)hasoccurredinpatientsbeingtreatedfor
spirochetalinfections.Effectsincludefever,chills,headache,malaise,muscleaches,leukocytosis,and
exacerbationofcutaneouslesions.TheJHRoccursin75to80percentofthosetreatedforsyphilis,54percent
ofthosetreatedfortickbornerelapsingfever,and82percentofthosetreatedforlousebornerelapsingfever.
PreventionoftheJHRinpatientsisoflimitedvaluethebestresultsarewiththeuseoftumornecrosisfactor
(TNF)antibodiesandsteroids.Pretreatmentwithacetaminophenormeptazinolmayreducethesymptomsand
duration[21].

Vertigohasbeenassociatedwithminocyclineandappearstobedoserelated.Morecommoninwomenthan
men,thismayappearduringthesecondorthirddayoftherapyandusuallyresolvesinonetotwodaysafter
discontinuingthedrug.Complaintsconsistofdizziness,ataxia,nausea,vomiting,andtinnitus.

Hematologiceffectsareveryuncommonbutmayincludehemolyticanemia,thrombocytopenia,neutropenia,
andeosinophilia.Other,lesscommonreactions,includeminocyclineinducedlupus[2224]andpericardial
effusions[25].

Nauseaandvomitinghavebeenreportedwithincreasedfrequencywithtigecycline(30and20percent)
comparedtotetracyclines[6].

DRUGINTERACTIONSTheabsorptionoftetracyclinescanbeimpairedbycoadministeredmineralsand
antacids(eg,calcium,magnesium,iron),lanthanum,anddairyincludingmilk.Tetracyclinescaninteractwith
oralisotretinoin,betalactams,andavarietyofotherdrugs.Specificdruginteractionsofthetetracyclinesand
managementsuggestionsmaybedeterminedbyusingLexiInteract,thedruginteractionsprogramincluded
withUpToDate.

SUMMARYANDRECOMMENDATIONS

Tetracyclinesinhibitbacterialproteinsynthesisbybindingreversiblytothe30Sribosomalsubunit.(See
'Mechanismofaction'above.)

Decreasedaccumulationofdrugwithinbacterialeadstoresistancedruguptakeisaffectedby
decreasinginfluxorincreasingefflux.(See'Resistance'above.)
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Thetetracyclinesareconsideredbroadspectrumbacteriostaticantibioticswithactivityagainstmany
aerobicgrampositiveandgramnegativebacteriaandatypicalpathogens,suchasmycoplasmaand
chlamydia.(See'Spectrumofactivity'above.)

Absorptionoftetracyclinesoccursprimarilyintheproximalsmallintestineandthestomachwithgood
distributionintotissuesandbodyfluids.(See'Pharmacodynamics/pharmacokinetics'above.)

Tetracyclinesshouldgenerallynotbeusedinpregnantwomenorchildrenundertheageofeightyears
unlessotherappropriatedrugsareineffectiveorcontraindicated.(See'Specialpopulations'above.)

Tetracyclinesaregenerallysafethemostcommonadverseeventsarerelatedtogastrointestinal
symptoms(eg,epigastricdiscomfortandnausea).(See'Adversereactions'above.)

UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

REFERENCES

1. SteinGE,CraigWA.Tigecycline:acriticalanalysis.ClinInfectDis200643:518.
2. Perdue,BE,Standiford,HC.Tetracyclines.In:AntimicrobialTherapyandVaccines,Yu,VL,Merigan,
TC,Barriere,SL(Eds),WilliamsandWilkins,Baltimore1999.p.981.
3. SchnappingerD,HillenW.Tetracyclines:antibioticaction,uptake,andresistancemechanisms.Arch
Microbiol1996165:359.
4. SpeerBS,ShoemakerNB,SalyersAA.Bacterialresistancetotetracycline:mechanisms,transfer,and
clinicalsignificance.ClinMicrobiolRev19925:387.
5. RobertsMC.Tetracyclinetherapy:update.ClinInfectDis200336:462.
6. Tigecycline(tygacil).MedLettDrugsTher200547:73.
7. ZhanelGG,HomenuikK,NicholK,etal.Theglycylcyclines:acomparativereviewwiththe
tetracyclines.Drugs200464:63.
8. WyethantibioticTygacilapprovedforbroadspectrum,earlyuse."ThePinkSheet"200567:12.
9. KleinNC,CunhaBA.Tetracyclines.MedClinNorthAm199579:789.
10. CentersforDiseaseControlandPrevention.SexuallyTransmittedDiseaseSurveillance,2006.Atlanta,
GA:U.S.DepartmentofHealthandHumanServices,November2007.
11. CentersforDiseaseControlandPrevention(CDC).Nonfatal,unintentionalmedicationexposuresamong
youngchildrenUnitedStates,20012003.MMWRMorbMortalWklyRep200655:1.
12. CraigWA.Pharmacokinetic/pharmacodynamicparameters:rationaleforantibacterialdosingofmiceand
men.ClinInfectDis199826:1.
13. SaivinS,HouinG.Clinicalpharmacokineticsofdoxycyclineandminocycline.ClinPharmacokinet1988
15:355.
14. Mandell,GL,Bennett,JE,Dolin,R,etal.PrinciplesandPracticesofInfectiousDiseases,6thed,
ChurchillLivingstone,Philadelphia2005.
15. AgwuhKN,MacGowanA.Pharmacokineticsandpharmacodynamicsofthetetracyclinesincluding
glycylcyclines.JAntimicrobChemother200658:256.
16. YimCW,FlynnNM,FitzgeraldFT.Penetrationoforaldoxycyclineintothecerebrospinalfluidofpatients
withlatentorneurosyphilis.AntimicrobAgentsChemother198528:347.
17. MacGowanAP.Tigecyclinepharmacokinetic/pharmacodynamicupdate.JAntimicrobChemother2008
62Suppl1:i11.
18. HeatonPC,FenwickSR,BrewerDE.Associationbetweentetracyclineordoxycyclineand
hepatotoxicity:apopulationbasedcasecontrolstudy.JClinPharmTher200732:483.
19. USFoodandDrugAdministration(FDA).FDAdrugsafetycommunication:Increasedriskofdeathwith
Tygacil(tigecycline)comparedtootherantibioticsusedtotreatsimilarinfections.
http://www.fda.gov/Drugs/DrugSafety/ucm224370.htm(AccessedonSeptember02,2010).
20. USFoodandDrugAdministration(FDA).FDAdrugsafetycommunication:FDAwarnsofincreasedrisk
ofdeathwithIVantibacterialTygacil(tigecycline)andapprovesnewboxedwarning.
http://www.fda.gov/Drugs/DrugSafety/ucm369580.htm(AccessedonMay05,2015).

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21. PoundMW,MayDB.ProposedmechanismsandpreventativeoptionsofJarischHerxheimerreactions.
JClinPharmTher200530:291.
22. SchliengerRG,BircherAJ,MeierCR.Minocyclineinducedlupus.Asystematicreview.Dermatology
2000200:223.
23. ColmegnaI,PerandonesCE,ChavesJG.Minocyclineinducedlupusandautoimmunehepatitis.J
Rheumatol200027:1567.
24. LawsonTM,AmosN,BulgenD,WilliamsBD.Minocyclineinducedlupus:clinicalfeaturesandresponse
torechallenge.Rheumatology(Oxford)200140:329.
25. ChristeC,RicouF,StollerR,VogtN.Minocyclineinducedpericardialeffusion.AnnPharmacother2000
34:875.

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GRAPHICS

Spectrumofactivityofthetetracyclines

Pathogens/syndromes
Rickettsialinfections(doxycycline)

Chlamydialinfections(doxycycline)

Traveler'sdiarrhea(doxycycline)

EarlyLymedisease(doxycycline)

Chloroquineresistantmalaria(doxycycline)

Acne

Amebiasis

Actinomycosis

Brucellosis

Borreliarecurrentis

Legionnaire'sdisease

Leptospirosis

Mycobacteriummarinum

Melioidosis

Mycoplasmapneumoniae

Meningococcalprophylaxis(minocycline)

MRSA(minocyclineortigecycline)

Nocardiosis

Pelvicinflammatorydisease

Staphylococcusaureus(minocyclineortigecycline)

Syphilis

Tularemia

Vibriovulnificus

VRE(susceptiblestrains)

Whipple'sdisease

Graphic58190Version2.0

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Dosingandadministrationoftetracyclines

Drug
Doxycycline 100mgIV/POevery12hoursNoadjustmentinrenaldysfunction

Tetracycline 250500mgPOevery6hourswithnormalrenalfunction.

250500mgPOevery12to24hourswithCrCl1050mL/min.

NotrecommendedwhenCrCl<10mL/min

Minocycline 100mgPOevery12hoursNoadjustmentinrenaldysfunction

Demeclocycline 150300mgPOevery12to24hoursAvoiduseinrenaldysfunction

Tigecycline 100mginitialdosethen50mgIVevery12hoursNoadjustmentinrenal
dysfunction

Graphic80309Version2.0

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Disclosures
Disclosures:DByronMay,PharmD,BCPSNothingtodisclose.DavidCHooper,MDConsultant/AdvisoryBoards:Bacterioscan
[Antimicrobials(Urinediagnosticunderdevelopment)]Cubist[Antimicrobials(Daptomycin,fidaxomycin,tedizolid,ceftolozane
tazobactam)]Shionogi[Antimicrobials(Antigramnegativebetalactamunderdevelopment)]Melinta[Antimicrobials(Antimicrobials
underdevelopment)]Cepheid[Antimicrobials(rapidgeneticdiagnostics)]FabPharma[Antimicrobials(Antimicrobialunder
development)].JenniferMitty,MD,MPHNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvetting
throughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.Appropriately
referencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy

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